The main objective of this long-standing research program, now in its 23rd year, is elucidation of principles governing development of the primate visual system. We perform this research in the macaque monkey, because its visual system is remarkably similar to that in human, containing features that are underdeveloped or absent in non-primate species and cannot be studied in more common animal models. In the next cycle of this grant we take advantage of newly emerging concepts about early development and powerful new methodological advances in molecular biology to examine intercellular interactions within and between various visual centers in primate embryos. Our unified hypothesis is that a number of primate-specific features, which emerge late in phylogeny but early in ontogeny, are specified by sets of genes and morphoregulatory molecules activated sequentially before birth. Thus, our goal is to analyze cellular mechanisms and the role of known and yet to be uncovered genes and gene products involved in: 1) the emergence of striate/extrastriate domains in the proliferative zones, thalamus and cortex; 2) the formation of the transient subpial granular layer and its role in the sublamination of layer IV in area 17; and 3) mechanisms of binocular segregation of the M & P visual subsystems. Each Aim consists of several interrelated experiments that include identifying, characterizing and inhibiting genes and morphoregulatory molecules that are expressed in embryonic primate visual targets prior to their innervation. Major approaches include selective reduction of the number of progenitor founder cells or various classes of target neurons in the cortex by timed X-irradiation during embryonic development, or by employing gain of function and dominant negative genetic approaches. This research will require a battery of methods, all of which have been tested in this laboratory. These include immunocytochemistry, in situ hybridization, confocal and electron microscopy, microarray chip technology, transneuronal tracers, as well as adenoviral gene transfer and in utero eletrophoretion. Understanding the uniqueness of the primate visual system will pari passu provide an essential bridge between fundamental research on non-primate species and the human condition; and hopefully will provide insight into genetic approaches for correcting congenital errors of visual development.